1. Field of the Invention
The invention relates generally to antimicrobial compositions, and more specifically to O-glycans containing terminal α1,4-linked N-acetylglucosamine residues, compositions containing such terminal α1,4-linked N-acetylglucosamine residues, and methods of using the compositions to prevent and/or treat bacterial infections.
2. Background Information
The stomach provides a very acidic environment that aids in the digestion of food, thus freeing up nutrients can be absorbed through the intestine. Generally, the cells lining the stomach are protected by a mucus layer, which is produced by cells of the stomach. Stomach ulcers (gastric ulcers) occur when a region of the stomach is exposed to the acid environment, thus resulting in the formation of a raw area or open sore in the lining of the stomach.
Stomach ulcers can occur due to increased production of acid in the stomach or by ingestion of acidic materials, and commonly occur in individuals who take non-steroid anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen, or drink too much alcohol or caffeine. About 70% of patients with gastric ulcers are infected with Helicobacter pylori (H. pylori). Most gastric ulcers that are not related to treatment with NSAIDs are accompanied by antral gastritis and H. pylori infection, whereas about 50% of gastric ulcers associated with these medications are not accompanied by H. pylori-associated gastritis. If patients with ulcers induced by NSAIDs are excluded, the prevalence of infection with H. pylori in patients with gastric ulcers is about 96%.
Helicobacter pylori is a microaerobic, gram negative and rod-shaped bacterium (bacillus) which lives on the lining of the stomach of about half the people on earth. It is considered to be a major cause of gastritis, chronic gastritis, gastric ulcer and duodenal ulcer. A relationship between Helicobacter pylori and diseases such as gastric cancer has also been reported. Development of a remedy for diseases caused by Helicobacter pylori is an important theme for maintaining health and well-being.
Antibiotics such as penicillin, tetracycline, cephalosporin and neuroquinone are known to be anti-Helicobacter pylori agents. However, although they exhibit antibacterial action against Helicobacter pylori, single administration of these agents is not sufficient to kill the bacteria. Recently, triple therapy has mainly been conducted using these antibiotics together with a bismuth agent and proton pump inhibitor. In addition, an anti-Helicobacter pylori agent containing benzohydroxamic acid has been proposed (Japanese Patent Application Laid-Open (JP-A) No. 11-189529). It is, however, inferior from the point of view of safety, because side effects such as diarrhea and vomiting can result.
An anti-Helicobacter pylori agent containing steryl glucopyranoside extracted from plants has also been proposed (JP-A No. 2003-73278). Further, an anti-Helicobacter pylori agent containing a component extracted from crude drugs such as Coptidis Rhizoma and a hydrogen carbonate of an alkali metal has been proposed (JP-A No. 2002-370995). However, these agents have side effects because they are not produced in the human living body and moreover, their antibacterial effects against Helicobacter pylori are insufficient. None of the above-described proposals includes disclosure about deterioration in the motility and abnormal morphology of Helicobacter pylori. 
The goal of treatment for gastric ulcers include pain relief, healing of the ulcer, prevention of complications, and prevention of recurrence of the ulcer. Complications due to untreated ulcers can include hemorrhage, perforation of the stomach wall, and obstruction due to scarring. In addition, about 2-3% of patients with stomach ulcers develop stomach cancer. Antibiotics are used to treat gastric ulcer patients infected with H. pylori. Treatment with antibiotics allows the ulcer to heal after the H. pylori infection is cured, and, if the treatment is successful, less than 5% of patients have a recurrence over the next year (as compared to a 60 to 80% recurrence rate if H. pylori infection is not cured).
H. pylori are difficult to eradicate from the stomach because the bacteria live deep in the mucous layer that covers the lining of the stomach, and it is difficult for antibiotics to penetrate into this mucous layer in sufficient concentrations to kill the bacteria. Generally, treatment with a single drug is ineffective in eliminating H. pylori infection. For example, amoxicillin has an eradication rate of less than 20%, and metronidazole has an eradication rate of less than 10%, while treatment with clarithromycin has an eradication rate of about 40%. As such, combination therapies are used, including combinations of two drugs (e.g., two antibiotics, or one antibiotic and one acid-lowering drug), and combinations of three drugs (e.g., two antibiotics and one acid-lowering drug). Eradication rates using a combination of two antibiotics range from 40% to 60%, and the best combinations of three drugs currently provide greater than 90% eradication of H. pylori infection in treated patients.
Unfortunately, H. pylori, like other bacteria, can become resistant to antibiotics, thus lowering the success rate of treatment. For example, resistance to metronidazole has been reported to be as high as 40% in some regions; and resistance to clarithromycin has been reported, though at a very low frequency (less than 2%). Since antibiotic resistance generally increases with time, there is concern that they may become progressively less effective for eradicating H. pylori and treating gastric ulcers. However, substances having sufficient antibacterial effects, being free from side effects, and having excellent safety, and their application technique have not yet been proposed. Thus, a need exists for compositions and methods of preventing and treating gastric ulcers.